Insight of fetal to adult hemoglobin switch: Genetic modulators and therapeutic targets.

The clinical heterogeneity of β-hemoglobinopathies is so variable that it prompted the researchers to identify the genetic modulators of these diseases. Though the primary modulator is the type of β-globin mutation which affects the degree of β-globin chain synthesis, the co-inheritance of α-thalassemia and the fetal hemoglobin (HbF) levels also act as potent secondary genetic modifiers. As elevated HbF levels ameliorate the severity of hemoglobinopathies, in this review, the genetic modulators lying within and outside the β-globin gene cluster with their plausible role in governing the HbF levels have been summarised, which in future may act as potential therapeutic targets.